The Cancer Genome Anatomies Projects (CGAP) Genetic Annotation Initiative (GAI) is an effort to expand the collection of available gene-based genetic analysis reagents for cancer research. Its goal is to enhance the utility of information and resources generated through the NCI's CGAP in genetic studies of families and populations. High resolution genetic analysis of the human genome promises to provide important insight into common disease susceptibility. To perform such analysis will require a collection of high-throughput, high-density analysis reagents. Using a set of sequence analysis tools, (the SNP pipeline) we have identified 12832 high-probability "candidate" SNPs among sequences contained in the 11- November 1999 UniGene release (#102) by examining publicly available expressed sequence tag (EST) chromatograms. PCR assays have been developed to validate a subset of these data. Using a pooled sample of 92 independent CEPH individuals, 6404 loci were examined by MALDI-TOF mass spectrometry and 3646 candidate SNPs validated. These variants are distributed among 2987 Unigene clusters of which 1124 are known genes. A total of 256 of the SNPs occur in coding regions and 118 are predicted to result in an amino acid substitution. Successfully validated variants are now being confirmed by examining transmission in CEPH pedigrees. When confirmed, the SNP is genetically mapped relative to the Cooperative Human Linkage Center (CHLC) reference maps. The above approach has also been applied to mouse EST data. Using this data 3284 candidate mouse SNPs have been identified To present the genetic variants in a format useful for the human genetics community we have constructed an integrated genetic/physical SNP map based on the CHLC/ABI Prism linkage marker set. Genetic map positions of reference markers are from the CHLC; physical map positions are from the GeneMap'98 Genebridge4 radiation hybrid map. More than 6500 of the candidate polymorphisms have been placed on an integrated genetic/physical map The integrated map, a Java-based tool for viewing candidate SNPs in the context of EST assemblies and a SNP search engine are available at our website: http://cgap.nci.nih.gov/GAI. We provide access to our SNP detection software for non-commercial use.